It is known that the preparation of vaccines commonly involves the steps of inactivating a live virus (whether it be attenuated, modified or killed), so that the virus thereafter can be introduced into a living being for inducing an active immune response (e.g., a protective response) in the being. The manufacture of such vaccines often encounters any of a number of practical constraints, which create a strain on health care systems. By way of example, in recent history, shortages of influenza vaccines have been experienced due to contamination problems in the manufacturing process. In the context of viral vaccines, one approach to the manufacture of such vaccines has been to grow the specific virus in advance of preparing the vaccine composition, such as by growing the virus in chicken eggs. The manufacture of viruses according to that approach can be expensive, and time consuming, especially considering that many times, one or two eggs may be necessary to yield each dose of vaccine. One classic approach to the manufacture of vaccines has been to inactivate a virus with formalin, binary ethylenimine, formaldehyde or combinations thereof. It is also typically necessary in the manufacture of vaccines to employ one or more preservatives to help prevent contamination by bacteria, fungus or both. Among the most widely employed preservatives have been phenol, 2-phenoxyethanol, or thimerosal (which contains mercury). Concerns have been expressed as to the potential efficacy, toxicity or mutagenicity of one or more of the above agents or other ingredients of vaccines. There has been a recognized resurgence in vaccine research in recent years, which has placed an even more acute demand upon vaccine manufacturers to address the above issues.
Swine Flu Virus is a negative segmented myxovirus. It has infected a significant portion of the human population. Improved vaccines are desired. Due to its widespread affect the there is a need for widespread distribution of precursors to vaccines and vaccines for this virus. One challenge is that many precursors to vaccines and vaccines require storage and transport at low temperatures, sub ambient temperatures. Thus it presents a challenge to provide such vaccines to populations located in places that do not have infrastructure for storage and transport of such precursors at sub ambient temperatures. To prepare vaccines, viruses are inactivated so that they do not infect the host and the antigens are stabilized, so that hosts inoculated with the inactivated viruses develop immunological responses. The United States Department of Agriculture has approved protocols for using binary ethylene-imine or formaldehyde to inactivate certain viruses for vaccine production. In U.S. Pat. Nos. 5,459,073; 5,811,099; and 5,849,517, there are disclosed preservative compositions that include a formaldehyde donor agent, and specifically, one or both of diazolidinyl urea or imidazolidinyl urea. That such compositions can be used in a vaccine is addressed in U.S. Pat. Nos. 5,811,099; and 5,849,517. Commonly owned and copending U.S. application Ser. No. 12/940,112 filed Nov. 5, 2010 titled “INACTIVATED VIRUS COMPOSITIONS AND METHODS OF PREPARING SUCH COMPOSITIONS”, now published as US 2011/0110975, discloses contacting a virus with a formaldehyde donor agent having a molecular weight that is greater than about 50 g/mol and less than about 400 g/mol for a period of time (e.g., at least about 12 hours) sufficient for de-activating the infectious component with the formaldehyde donor agent and for preserving at least a portion of the surface antigens to form a deactivated virus and the resulting composition. This application is incorporated herein by reference.
Notwithstanding the foregoing, there remains a need in the art for safer and less toxic inactivated live virus compositions useful in vaccines, more specifically, veterinary vaccines, and still more specifically, inactivated-viral swine vaccines, which can be produced in high yield, with inconsequential toxicity or other potential undesired side effects. What is further needed are vaccine precursors and vaccines that can be stored and transported at ambient temperatures and processes for their production, transport and storage at ambient temperatures. What is needed are compositions that can be manufactured in an efficient manner, that contain components which enhance the disinfectant and antimicrobial properties of the vaccine precursors, that exhibit hemagglutination equal to or better than industry standards, compositions that do not exhibit a loss in titer and are relatively non-toxic.